Baraitser-Winter cerebrofrontofacial syndrome

Baraitser-Winter cerebrofrontofacial syndrome (BWCFF), also known as Baraitser-Winter syndrome, is a rare congenital disorder characterized by a distinctive combination of craniofacial abnormalities, brain malformations, and ocular anomalies. The syndrome is caused by heterozygous missense mutations in the ACTB gene (encoding beta-actin) or the ACTG1 gene (encoding gamma-actin), both of which play critical roles in cytoskeletal function and cell migration during embryonic development. The condition was historically described as two separate entities — Baraitser-Winter syndrome and cerebrofrontofacial syndrome — before being unified under the current name. Key clinical features include a characteristic facial appearance with hypertelorism (widely spaced eyes), broad nose with a wide nasal bridge, ptosis (drooping eyelids), and a prominent metopic ridge or trigonocephaly. Brain malformations are a hallmark of the condition, most notably lissencephaly or pachygyria (abnormal brain gyral patterns), particularly affecting the frontal lobes, as well as anterior-predominant cobblestone-like cortical malformations. Ocular colobomas (iris or retinal), sensorineural hearing loss, seizures, and intellectual disability of variable severity are frequently observed. Short stature and cardiac defects may also occur. There is currently no cure or disease-specific treatment for Baraitser-Winter cerebrofrontofacial syndrome. Management is supportive and multidisciplinary, focusing on the individual's specific symptoms. This may include antiepileptic medications for seizure control, surgical correction of ptosis or other structural anomalies, hearing aids or cochlear implants for hearing loss, and developmental therapies including speech, occupational, and physical therapy. Regular ophthalmologic, audiologic, and neurologic follow-up is recommended. Genetic counseling is important for affected families.

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